Thymoma‐associated multi‐organ autoimmunity: A case of graft‐versus‐host disease‐like erythroderma complicated by Good syndrome successfully treated by thymectomy

Thymoma‐associated multi‐organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft‐versus‐host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD‐like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD‐like erythroderma.     

Ultrastructural changes of the air–blood barrier in mice after intratracheal instillation of lipopolysaccharide and ultrafine carbon black particles

Epidemiological studies have indicated associations between exposure to increased concentrations of ambient ultrafine particles and adverse health effects especially in susceptible individuals. To ellucidate the mechanisms underlying the findings from epidemiological studies, mice pretreated with lipopolysaccharide (LPS) (acute lung injury model) were intratracheally instilled with ultrafine carbon black particles (UFCB), and the air–blood barrier was observed to examine the translocation pathway of UFCB from the lung into the systemic circulation. In addition, lung toxicity induced by the intratracheal instillation of LPS and UFCB was studied with the use of electron microscope. LPS treatment induced acute inflammatory changes with increased number of activated macrophages and neutrophils in the degenerated alveolar walls. UFCB were demonstrated on or in the denuded basement membrane in the air–blood barrier; these findings were associated with edematous changes and fragmentation of the cytoplasms of alveolar epithelial cell type 1, and the damages of alveolar epithelial cell type 1 were frequently observed in the close vicinity of the clumps of UFCB. These findings suggest that translocation of the exposed ultrafine particles may be enhanced in the lung tissues with acute inflammatory changes.     

Does distal tibiofibular joint mobilization decrease limitation of ankle dorsiflexion?

Limitation of ankle motion is in many cases treated by joint mobilization (JM), a kind of manual physical therapy technique. Until now, the JM approach has mainly focused on the talocrural joint, with less attention to the distal tibiofibular joint. We applied cyclic loading to the lateral malleolus as in JM in order to clarify the relationship between the dorsiflexion angle and the excursion of the lateral malleolus. Seven normal, fresh-frozen cadaver legs were used. To each specimen, cyclic loading with a 30 N force was applied 1000 times to the lateral malleolus at a speed of 15 N/s. The displacement of the lateral malleolus was measured with a magnetic tracking system. The maximum dorsiflexion angle was measured before and after cyclic loading. After the first 100 and 1000 times of cyclic loading, the tibia was displaced 0.44 ± 0.30 mm and 0.75 ± 0.36 mm, respectively, and the fibula was displaced 0.44 ± 0.28 mm and 0.92 ± 0.39 mm, respectively. The average dorsiflexion angle increased from 14.36 ± 7.51° to 16.74 ± 7.21° after cyclic loading (P < 0.05). Movement of the distal tibiofibular joint led to a significant increase in the range of ankle dorsiflexion. These results suggest that tibiofibular JM would be effective for limitation of ankle dorsiflexion.     

Factors on delayed recovery of otitis media with effusion in children--clinical and bacteriological study

The resolution of middle ear effusions (MEE) of children with otitis media with effusion (OME) who underwent myringotomy for the bacteriological examination was analyzed in terms of the culture results and the clinical features. The present study consisted of 193 children (258 ears), and the MEE from 77 ears (30%) were culture positive and the respiratory pathogens were detected from 44 ears (17%). Each child was then assigned to receive either a more than two-week course of antibiotics, cefaclor (CCL) or not. At one month following entry, 53 (55%) out of 97 ears in CCL-treated group were effusion-free compared with 31 (40%) out of 78 ears in the control group (P less than 0.05). In the control group, the resolution of MEE was significantly poor in the recurrent cases and the cases with pathogen positive-MEE. The presence of accompanying diseases such as adenoid vegetation, chronic sinusitis and allergy, however, was not related to the resolution of MEE. On the other hand, the cure rate of the cases with pathogen positive-MEE and recurrent cases in the CCL-treated group showed significant improvement. Furthermore, the cases accompanying adenoid vegetation and chronic sinusitis tended to become effusion-free after the antibiotic treatment. Therefore, the persistent bacterial infection in the middle ear and/or surrounding organs such as adenoid plays possibly an important role in the delayed recovery of OME. Antibiotics treatment could increase, to some extent, the resolution of MEE in cases with OME.     

Changes in folate concentration in Yoshida sarcoma after administration of leucovorin or cisplatin

Both leucovorin (LV) and cisplatin ( cis-dichlorodiammine platinum II, CDDP) act as modulators of 5-fluorouracil (5-FUra) by increasing the intracellular concentration of reduced folate. We measured intracellular folate levels following the administration of LV or cisplatin in tumor-bearing rats to determine the optimal schedules for their use as 5-FUra modulators. Donryu rats were inoculated with Yoshida sarcoma cells on the right flank. Seven days after tumor inoculation, the animals were injected with LV or CDDP. The kinetic and dose-related changes in intracellular folate concentration were analyzed by means of a binding assay. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after administration of LV and remained significantly high until 8 h after administration. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after cisplatin administration, then decreased to a rather low level 8 h after, and to a significantly lower level than baseline 24 h after administration. The folate levels in the tumor tissue increased in proportion to the dose of LV, but did not increase when the dose of cisplatin was increased from 1 mg/kg to 8 mg/kg. Repeat high-dose administration of LV and repeat low-dose administration of cisplatin are advocated when they are used as modulators of 5-FUra.     

Clinical evaluation of contact Nd.YAG laser conization for cervical intraepithelial neoplasia of the uterus.

Contact Nd.YAG laser conization (laser cone) was performed in 500 patients with preoperatively diagnosed cervical intraepithelial neoplasia (CIN) since September 1983. The patients treated were followed for 12 to 96 months (39.2 months on average). Average operation time was 11.4 minutes. A cure with laser cone (single treatment) was achieved in 98.6%, including cases with microinvasive and invasive carcinoma, post-operatively. There were only 7 (1.4%) true residual cases of 47 cases (9.4% of total cases) with incomplete excision. High spontaneous cure rates (85.1%) in cases with incomplete excision are considered to be a characteristic of laser cone treatment. The contact laser cone method also got good specimens for histologic examinations. They gave a large amount of information for our follow-up. The results indicate that contact Nd.YAG laser conization for CIN is an excellent conservative therapy from the point of cure rate, safety, indication, operation time and cone specimen, even compared with CO2 laser conization.     

Human monocytes show chemotaxis in response to cholesteatoma debris]

Using a microchamber technique, we tested cholesteatoma debris and certain of its constituents for effects on the migration of human peripheral blood monocytes and polymorphonuclear leukocytes. Cholesteatoma debris induced significant migration of monocytes. When the individual constituents of cholesteatoma debris, i.e., alpha-keratin, cholesterol, lauric acid and lipopolysaccharides, were tested for monocyte chemotaxis, only alpha-keratin induced significant monocyte migration. alpha-keratin extracted from the cholesteatoma debris with 8 M urea also induced migration of monocytes with a bell-shaped dose-response curve, which is frequently encountered with chemoattractants. Therefore, cholesteatoma debris and one of its components, alpha-keratin, are potent chemoattractants for human monocytes. On the other hand, cholesteatoma debris showed no significant chemotactic effect on polymorphonuclear leukocytes. Based on the present and our previous results, cholesteatoma debris acts on monocytes/macrophages as a strong chemotactant, a potent activating (priming) factor, and an inducer of production of tumor necrosis factor, which is a bone-resorbing cytokine. Therefore, we concluded that macrophages induced by cholesteatoma debris may play an important role in the pathogenesis of bone resorption in cholesteatoma otitis.     

Neoadjuvant Chemotherapy with Etoposide, Leucovorin, 5-Fluorouracil and Cisplatin for Advanced Esophageal Squamous Cell Carcinoma

Eighteen patients with invasive periadventitial tissue (T4)or distant lymph node metastatic (M1,LYM) squamous cell carcinomawere entered into a pilot study of neoadjuvant chemotherapywith etoposide (50 mg/m²/day, days 1–5), leucovorin (30mg/body/day, days 2–5), 5-fluorouracil (5-FU; 400 mg/m²/day,days 2–5) and cisplatin (100 mg/m²–day, day 1) (ELFP).The overall response rate was 56%. The response rates in theT4 tumor and M1, LYM patients were 56 and 50%, respectively.Radical esophagectomies were performed on six of 17 patientswho had completely recovered from the chemotherapy, a resectabilityof 35%. Histologically, the primary tumor was moderately toslightly effective, and the lymph nodes markedly to moderatelyeffective. Histologic responses in the lymph nodes were differentfrom those in the primary tumors and in each node. There werefour chemo-surgically related deaths. Median survival timesin responding and non-responding patients were nine and threemonths, respectively. In conclusion, neoadjuvant chemotherapywith ELFP appears to be effective against esophageal squamouscell cancer with periadventitial tissue invasion or distantlymph node metastasis. Chemo-surgically related deaths werehowever, 22%, showing neoadjuvant chemotherapy to necessitateextremely careful attention to the medical and surgical managementof patients.     

Generation of human monoclonal antibodies recognising membranous antigens of the lung adenocarcinoma cell line A549 using an AMeX immunohistostaining method.

Four monoclonal antibodies (MAbs) from hybridoma obtained by in vitro stimulation of regional lymph node lymphocytes from lung cancer patients and electrofusion of the stimulated cells with murine or human-mouse myeloma cells were reactive to lung cancer cells in enzyme-linked immunoabsorbent assay, and to lung cancer tissue in immunohistochemical analysis using acetone-methyl benzoate-xylene (AMeX) fixed tissue and in immunofluorescence analysis. Three of the MAbs (designated ZLG40, 27D57 and 28K29) recognised cell-surface antigens of the lung adenocarcinoma cell line A549 and the remaining one (designated 29D38) recognised nuclear membrane antigens of the same cell line. The three surface-binding MAbs showed a significant complement-dependent cytotoxicity (CDC) to the A549 cells, but the membrane-binding 29D38 showed no CDC to the A549 cells. Western blotting of the extracts of the A549 or PC6 (small-cell lung cancer) cell lines by the four MAbs showed a 28K29 antigen band at M(r) of approximately 600,000 (+/- 2-ME), a ZLG40 antigen band at M(r) 50,000 (+/- 2-ME), and one 29D38 antigen band at M(r) of more than 1,000,000 (-2-ME) and M(r) between 20,000 and 80,000 (+2-ME), but no detectable band for 27D57 antigen.     

Is decidua affected in gestational hypertension? Indication by elevated PP14 levels

The serum concentration of placental protein 14 (PP14) was measured by radioimmunoassay in 129 apparently healthy pregnant women at 33-40 weeks, and the results were compared with those of 40 women with gestational hypertension either with or without proteinuria at similar weeks. In normal pregnancy, maternal serum PP14 levels decreased towards term. Therefore, the results were expressed as multiples of the normal median for each week. In gestational hypertension, the values were higher than normal (p less than 0.001): they were above the normal median in 32 (80%) cases (p less than 0.005), and above the normal 90th percentile in 15 (38%) cases (p less than 0.001). The presence or absence of proteinuria did not affect the result. Since recent findings suggest that PP14 is synthesized by late pregnancy decidua and not by the placenta, our results suggest that decidua may be affected in gestational hypertension.